H Stass1, D Kubitza. 1. Pharma Research Centre, Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany. Heino.Stass.hs@bayer-ag.de
Abstract
OBJECTIVE: To investigate the plasma and urinary pharmacokinetics, safety and tolerability of theophylline and moxifloxacin after single and repeated doses of either compound administered alone or concomitantly with the other. DESIGN: This was a randomised, multiple-dose, period-balanced, 3-way crossover study in healthy volunteers. PARTICIPANTS: 12 nonsmoking healthy volunteers, 21 to 30 years of age were included in this study. METHODS: The investigational medications, all given orally, were as follows: treatment A, moxifloxacin 200mg alone; treatment B, theophylline 400mg alone; treatment C, theophylline 400mg plus moxifloxacin 200mg. Each drug or combination was given twice daily on days 2 to 4 of the 5-day study period and as single morning doses on days 1 and 5. The study periods were separated by 1-week washout intervals. The plasma and urinary pharmacokinetics of moxifloxacin and theophylline were characterised after the first (morning of day 1) and eighth (morning of day 5) doses. RESULTS: At steady state, the plasma pharmacokinetics of theophylline for treatments B and C proved equivalent in terms of maximum concentration (Css(max)) and bodyweight- and dose-normalised Css(max) lestimated true ratio 96%, 90% confidence interval (CI) 87 to 105%] and also in terms of area under the concentration-time curve from 0 to 12 hours (AUCss(tau)) and normalised AUCss(tau) (ratio 95%, 90% CI 85 to 107%); the median times to Cmax(tmax) were also similar (5.0 and 6.0 hours for treatments B and C, respectively). The plasma pharmacokinetics of moxifloxacin for treatments A and C were equivalent with respect to Css(max) (estimated true ratio 109%, 90% CI 97 to 123%) and AUCss(tau) (ratio 104%, 90% CI 100 to 108%); the median tmax values were also similar (0.5 and 1.0 hour for treatments A and C, respectively). The treatments were well tolerated. CONCLUSIONS:Moxifloxacin - in contrast to some older quinolones - does not interact pharmacokinetically with theophylline, confirming preclinical results on the absence of cytochrome P450-mediated metabolism.
RCT Entities:
OBJECTIVE: To investigate the plasma and urinary pharmacokinetics, safety and tolerability of theophylline and moxifloxacin after single and repeated doses of either compound administered alone or concomitantly with the other. DESIGN: This was a randomised, multiple-dose, period-balanced, 3-way crossover study in healthy volunteers. PARTICIPANTS: 12 nonsmoking healthy volunteers, 21 to 30 years of age were included in this study. METHODS: The investigational medications, all given orally, were as follows: treatment A, moxifloxacin 200mg alone; treatment B, theophylline 400mg alone; treatment C, theophylline 400mg plus moxifloxacin 200mg. Each drug or combination was given twice daily on days 2 to 4 of the 5-day study period and as single morning doses on days 1 and 5. The study periods were separated by 1-week washout intervals. The plasma and urinary pharmacokinetics of moxifloxacin and theophylline were characterised after the first (morning of day 1) and eighth (morning of day 5) doses. RESULTS: At steady state, the plasma pharmacokinetics of theophylline for treatments B and C proved equivalent in terms of maximum concentration (Css(max)) and bodyweight- and dose-normalised Css(max) lestimated true ratio 96%, 90% confidence interval (CI) 87 to 105%] and also in terms of area under the concentration-time curve from 0 to 12 hours (AUCss(tau)) and normalised AUCss(tau) (ratio 95%, 90% CI 85 to 107%); the median times to Cmax(tmax) were also similar (5.0 and 6.0 hours for treatments B and C, respectively). The plasma pharmacokinetics of moxifloxacin for treatments A and C were equivalent with respect to Css(max) (estimated true ratio 109%, 90% CI 97 to 123%) and AUCss(tau) (ratio 104%, 90% CI 100 to 108%); the median tmax values were also similar (0.5 and 1.0 hour for treatments A and C, respectively). The treatments were well tolerated. CONCLUSIONS:Moxifloxacin - in contrast to some older quinolones - does not interact pharmacokinetically with theophylline, confirming preclinical results on the absence of cytochrome P450-mediated metabolism.
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